Submissions for variant NM_000057.4(BLM):c.3128C>A (p.Ala1043Asp)

gnomAD frequency: 0.00421  dbSNP: rs2229035

Total submissions: 13

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000123849	SCV000167192	benign	not specified	2014-02-18	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000230670	SCV000283131	benign	Bloom syndrome	2024-02-01	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000123849	SCV000340424	benign	not specified	2016-03-15	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000123849	SCV000593637	benign	not specified	2018-02-27	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000572905	SCV000672888	likely benign	Hereditary cancer-predisposing syndrome	2018-12-19	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Counsyl	RCV000230670	SCV000794567	likely benign	Bloom syndrome	2017-09-29	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000230670	SCV001275190	benign	Bloom syndrome	2017-11-15	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000123849	SCV001748748	benign	not specified	2021-06-28	criteria provided, single submitter	clinical testing	Variant summary: BLM c.3128C>A (p.Ala1043Asp) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00088 in 249668 control chromosomes, predominantly at a frequency of 0.012 within the African or African-American subpopulation in the gnomAD database, including 1 homozygotes. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 3.39 fold of the estimated maximal expected allele frequency for a pathogenic variant in BLM causing Bloom Syndrome phenotype (0.0035), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. At least one publication reports experimental evidence evaluating an impact on protein function. These results showed no damaging effect of this variant. Six clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV001800416	SCV002046793	benign	not provided	2021-04-01	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000572905	SCV002530050	benign	Hereditary cancer-predisposing syndrome	2020-10-23	criteria provided, single submitter	curation
Fulgent Genetics, Fulgent Genetics	RCV000230670	SCV002807132	likely benign	Bloom syndrome	2021-08-26	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV000230670	SCV004016386	benign	Bloom syndrome	2023-07-07	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV000230670	SCV002090519	likely benign	Bloom syndrome	2018-04-05	no assertion criteria provided	clinical testing